Male sexual behavior and human papillomavirus DNA: key risk factors for cervical cancer in Spain.

BACKGROUND: It is now established that certain types of human papillomaviruses (HPVs) are the sexually transmitted agents etiologically linked to cervical cancer. Studies assessing the contribution of the male's sexual behavior and genital HPV DNA status to the risk of development of cervical neoplasia in sexual partners have yielded inconsistent results. PURPOSE: This study evaluates the role of men's sexual behavior and the presence of HPV DNA in the penis on the development of cervical cancer in their sexual partners in Spain, a low-risk area for cervical neoplasia. METHODS: Husbands (n = 633) of women participating in two case-control studies of cervical neoplasia were interviewed to obtain information on lifestyle habits, including sexual practices. Cytologic samples were taken from the distal urethra and the surface of the glans penis of 183 husbands of case women and of 171 husbands of control women. These samples were analyzed by a polymerase chain reaction-based system using a generic probe and 25 type-specific probes for the detection and typing of HPV DNA. Serologic specimens were also obtained and analyzed for antibodies to Chlamydia trachomatis, Treponema pallidum, herpes simplex virus type II, and Neisseria gonorrhoeae. RESULTS: The presence of HPV DNA in the husbands' penis conveyed a fivefold risk of cervical cancer to their wives (adjusted odds ratio [OR] for HPV DNA positivity = 4.9; 95% confidence interval [CI] = 1.9-12.6). The risk of cervical cancer was strongly related to HPV type (adjusted OR for HPV type 16 = 9.0; 95% CI = 1.1-77.5), to the husbands' number of extramarital partners (adjusted OR = 11.0; 95% CI = 3.0-40.0; for > or = 21 women versus one), and to the number of prostitutes as extramarital sexual partners (adjusted OR = 8.0; 95% CI = 2.9-22.2; for > or = 10 women versus none). Presence of antibodies to C. trachomatis (adjusted OR = 2.6; 95% CI = 1.4-4.6) and an early age at first sexual intercourse of the husband (adjusted OR = 3.2; 95% CI = 1.7-5.9; for < or = 15 years versus > or = 21 years) were also associated with cervical neoplasia in the wife. After adjustment for these variables and for the wife's pack-years of smoking, the husband's smoking was moderately associated with cervical cancer in his wife (adjusted OR = 2.5; 95% CI = 1.4-4.4; for > or = 26.2 pack-years versus none). CONCLUSIONS: The study supports the role of men as vectors of the HPV types that are related to cervical cancer. Life-time number of female sexual partners, number of female prostitutes as sexual partners, and detection of HPV DNA in the penis of husbands are all surrogate markers of exposure to HPV during marriage. IMPLICATIONS: Men who report multiple sexual partners or who are carriers of HPV DNA may be vectors of high-risk HPV types and may place their wives at high risk of developing cervical cancer. Prostitutes are an important reservoir of high-risk HPVs.

Human papillomavirus DNA and antibodies to human papillomaviruses 16 E2, L2, and E7 peptides as predictors of survival in patients with squamous cell cervical cancer.

PURPOSE: To assess whether human papillomavirus (HPV) DNA detection in cervical cancer specimens, or antibodies to selected HPV 16 peptides are predictors of tumor recurrence and long-term survival in patients with squamous cell invasive cervical cancer. SUBJECTS AND METHODS: Four hundred seventy-one cases included in two population-based case-control studies underwent follow-up evaluation. The survival and cause of death were ascertained for 410 cases (87%), with a median follow-up time of 4.6 years after diagnosis. HPV DNA was assessed using an L1 polymerase chain reaction (PCR)-based system and Southern hybridization (SH) on scraped cytologic specimens or biopsies. HPV 16 antibodies to E2, L2, and E7 peptides were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS: Clinical stage was the only independent prognostic factor for recurrence or survival. Although seropositivity to HPV 16 E7/3 peptide predicted a twofold excess risk of mortality (adjusted hazards ratio [HRa] = 2.0; 95% confidence interval [CI], 1.2 to 3.3), the association was restricted to stage I (HRa = 6.6; 95% CI, 1.2 to 37.6) and II (HRa = 5.9; 95% CI, 2.1 to 16.5) patients. The presence of HPV DNA (HRa = 0.9; 95% CI, 0.5 to 1.5), different estimates of the HPV viral load and the HPV type identified were not predictors of tumor recurrence or survival. CONCLUSION: The presence of antibodies to HPV 16 E7 proteins is of prognostic value in early-stage cervical cancer. Our results provide strong evidence that detection and typing of HPV DNA in cervical cells or tissues is not a prognostic factor for recurrence or survival.

Risk factors for cervical intraepithelial neoplasia grade III/carcinoma in situ in Spain and Colombia.

A case-control study of 525 histologically confirmed cases of cervical intraepithelial neoplasia grade III and 512 controls was done in Spain and Colombia to assess the role of various risk factors taking into account the effect of human papillomavirus (HPV). The presence of HPV DNA, assessed by a polymerase chain reaction-based method, was the strongest risk factor identified. In Spain the adjusted odds ratio (OR) and 95% confidence interval (CI) (numbers in parentheses) were 56.9 (24.8-130.6) and, in Colombia, were 15.5 (8.2-29.4). In addition to HPV, the multivariate analysis revealed independent effects of early age at first intercourse (in Spain ORa, 4.3; 95% CI, 2.0-9.3 for ages < 17 versus 20+ years and in Colombia ORa, 9.0; 95% CI, 2.6-30.9 for ages < 14 versus 20+ years), and antibodies to Chlamydia trachomatis (in Spain ORa, 2.3; 95% CI, 1.1-4.5; and in Colombia ORa, 1.7; 95% CI, 1.1-2.7). High parity showed a significant effect only in Colombia (ORa, 2.0; 95% CI, 1.0-5.0 for > or = 6 versus 1) while number of partners of the woman and specially of her husband showed a strong effect in Spain only (ORa, 6.9; 95% CI, 3.1-15.3 for partners of the husband > or = 21 versus 1-5). Smoking and use of oral contraceptives did not show significant or consistent associations. Among HPV-DNA positive women early age at first intercourse and high parity increased the risk of cervical intraepithelial neoplasia III but the effect was statistically significant only for the former.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomised double-blind study comparing tropisetron alone and in combination with dexamethasone in the prevention of acute and delayed cisplatin-induced emesis.

In a randomised, double-blind and parallel-design multicentre study, 282 chemotherapy-naive cancer patients received tropisetron 5 mg intravenously (i.v.) before high-dose cisplatin on day 1, and oral tropisetron 5 mg daily on days 2-6, in combination with either placebo (n = 143) or dexamethasone (n = 135), given i.v. on day 1 and orally on days 2-6. Complete protection from acute vomiting/nausea was achieved in 76.3%/79.3% of patients receiving the combination and in 55.2%/61.5% of those receiving tropisetron alone. Complete protection on days 2-6 from delayed vomiting/nausea was obtained in 60%/60% and 39.2%/40.6%, respectively. Tropisetron in combination with dexamethasone is safe and more effective than tropisetron alone in the prevention of both acute and delayed cisplatin-induced emesis.

Phase II trial of carboplatin in combination with etoposide in locally advanced large cell carcinoma and adenocarcinoma of the lung.

A total of 18 patients with locally advanced (Stage III) adenocarcinoma and large cell undifferentiated carcinoma of the lung, previously untreated, were enrolled in a Phase II trial. Treatment consisted of carboplatin 325 mg/m2, day 1 and etoposide 100 mg/m2 on days 2 and 3. All patients were evaluable for response. Of these, one patient had a partial response (5.5%; confidence interval 0-24%). Toxicity comprised mainly leukopenia and anaemia. Other toxicities were mild. This Phase II study evidenced a poor response rate for these regimes on adenocarcinoma and large cell undifferentiated carcinoma of the lung.

A breast cancer case-control study in Girona, Spain. Endocrine, familial and lifestyle factors.

This study was designed to explore risk factors for breast cancer with emphasis on the detection of clinical markers of the hormonal imbalance during the perimenarche. Three hundred and thirty women diagnosed with breast cancer and 346 population controls were identified and interviewed in Girona, Spain between 1986 and 89. Cases were more likely than controls to have had long menstrual periods in the first 5 years after menarche [odds ratio (OR) = 3.0], to experience menopause at a late age (OR = 1.5) and to report acne during adolescence (OR = 1.6). Family history of breast cancer was associated with an increased risk (OR = 2.3). Cases reported a lower use of drug treatments for anxiety and sleep disorders than controls. Moderate alcohol drinkers and smokers were at lower risk for breast cancer. No statistically significant association with breast cancer was observed for number of children, age at last pregnancy, oral contraceptive use, hormonal treatment after menopause and weight perception during the teenage years. Hormonal changes in the years following menarche may be relevant to breast cancer risk. The roles of menstrual period length and acne during adolescence should be further explored.

Cervical cancer: incidence and survival in migrants within Spain.

STUDY OBJECTIVE: This study examined the incidence of cervical cancer and survival rates according to migrant experience of women from different regions of Spain to Girona, Catalonia (Spain). DESIGN: Using data from the population based cancer registry of Girona for the period 1980-89, crude and age adjusted incidence rates were calculated for local-born and first generation migrants from other Spanish regions. The age standardised rate ratio (SRR) was calculated and Cox's regression model was used to adjust survival according to migrant status for age and stage at diagnosis. MAIN RESULTS: The incidence of cervical cancer was significantly higher in first generation Spanish migrants compared with locally born women (SRR: 2.02; 95% CI 1.40:2.92). The stage at diagnosis was more advanced among migrants. Survival probability was significantly associated with stage at diagnosis, but age and region of birth were not. CONCLUSIONS: Migrants from the southern Spanish regions show a twofold excess in the incidence of cervical cancer compared with the Girona-born female population. Cases of cervical cancer in migrants are diagnosed at a more advanced stage and as a consequence have a poorer prognosis.

Catalonia WHO Demonstration Project on Palliative Care Implementation 1990-1995: results in 1995.

A global, comprehensive, publicly planned and financed program to implement palliative care was designed by the Department of Health of Catalonia (6 million inhabitants. Planned in collaboration with the cancer unit of the WHO in 1989, the program was implemented in 1990-1995. It included specific services, measures general resources, education and training, organizational and educational standards, opioid availability, legislation and evaluation. The aims included coverage for cancer, AIDS, geriatric and other conditions, equity, quality, reference, and satisfaction for patients, families, and professionals. The results in 1995 include the implementation of 18 hospital support teams and 19 Units, with a total of 350 beds, 42 home-care teams. The coverage for cancer and AIDS is around 40%, and 44/55 (80%) districts have a specific team. Palliative care implementation has been completely publicly financed, with a total yearly investment of 2,200 million ptas. Eighty percent of this has been saved through radical changes in costs and the pattern of the use of resources. Palliative care implementation has demonstrated efficacy in the care of the patients and families, efficiency in the provision of care, and cost-benefit in the regional global approach. It adds qualitative and organizational values to the health-care system. Its implementation must be prioritized and planned by the health administration, not only to improve the quality of care for advanced and terminal patients, but also to improve the global efficiency and appropriate use of resources in the public health system.

Neurological assessment of high grade astrocytomas following high dose radiotherapy as sole treatment.

Between January 1985 and June 1991, 19 patients, in whom the site and extension of the tumour prevented surgical excision, were treated with high dose radiotherapy as sole treatment for high grade astrocytomas. Quality of life, according to functional capacity, was measured prospectively before treatment and 4 weeks later. High dose radiation improved the functional capacity in only four of the patients (21%). The mean duration of improvement was 12 weeks and median survival 22 weeks (range 4-80). We conclude that high dose radiotherapy is not very useful and is probably not justified in this group of patients.

[Perception of the causes of cancer and its prevention in women of Girona]. / La percepción de las causas del cáncer y de su prevención en las mujeres de Girona.

BACKGROUND: To analyze the perception of causes and prevention of cancer among women, from Girona, Spain, as well as to assess the knowledge of initial symptoms and participation in cancer screening activities. SUBJECTS AND METHODS: Crossectional survey with the following items: cancer risk factors, initial symptoms, perceived susceptibility, knowledge and practice of screening, beliefs regarding prevention and treatment of cancer, intention to attend screening tests and socio-demographic variables. A stratified random sample of 408 women aged 40 to 70 from two counties in Girona, Spain was selected. RESULTS: More than 80% of women identified tobacco, radioactivity and other environmental factors as causes of cancer, being the alcohol identified by 70% of women. It was clearly observed that a high level of these women (97.5%) considered a lump in the breast as an initial symptom of cancer, whereas only a 6.6% thought it was always due to cancer. With regard to cancer screening, 21.9% of women have ever practiced a mammography, 28.5% a cervical citology with Papanicolaou staining and 53.2% self-breast examinations. All these screening activities were inversely associated to age (p < 0.05) and directly to educational level (p < 0.05). CONCLUSION: A high knowledge regarding the causes of cancer with the exception of diet was observed in women from Girona, Spain. Knowledge and participation in screening activities is still low in practice of population cancer screening programmes.

[Breast cancer and heredity: results of a population case-control study in Girona]. / Cáncer de mama y herencia: resultados de un estudio poblacional de casos y controles en Girona.

BACKGROUND: To characterise the relationship between breast cancer and different aspects of the reproductive life, use of drugs and alcohol by family history of breast cancer. PATIENTS AND METHODS: From the cancer registry of Girona, Spain, 330 women were identified with histologically confirmed breast cancer during 1986-1989. For each case, a control woman was selected from a random sample of the population living in the matched area to the case by age (+/- 5 yr.). The information was collected by a personal interview and included: family history of breast cancer, reproductive history, presence of acne during the teenage years, use of oral contraceptives and drugs for sleep and anxiety disorders, and alcohol consumption. RESULTS: 18.5% of breast cancer cases and 8.9% of all controls had a family history of breast cancer. Family history on a first degree relative (mother or sister) was present in 10.6% of the cases and 2.8% of controls, which represented an odds ratio for breast cancer of 3.7 (95% CI, 1.8-7.8) higher than the general population. Women with a first degree family history of breast cancer were at higher risk for breast cancer if they had a history of acne during the teenage period (OR = 2.4; 95% CI, 1.1-5.2) and if they referred long menstrual periods in the early years of menarche (OR = 3.1; 95% CI, 1.3-7.0). Women with no family history had a higher breast cancer risk if they had a late menarche, long menstrual periods, late first full term pregnancy, and history of acne during puberty. Alcohol consumption and use of drugs for anxiety and sleep disorders were associated with a decreased risk of breast cancer. CONCLUSIONS: First degree family history of breast cancer seems to be the best risk indicator for developing breast cancer. Long menstrual periods and presence of acne during puberty may indicate hormonal imbalance that act independently of the family history in breast cancer development.

[The risk of breast cancer in Catalonia]. / El riesgo del cáncer de mama en Cataluña.

BACKGROUND: To evaluate the risk of developing breast cancer among Catalan women and to estimate the number of new cases of this tumor that appear annually in Catalonia (north-east of Spain). MATERIAL AND METHODS: The incidence rates of breast cancer were used in the period 1985-1989 proceeding from the population-based cancer registries of Tarragona and Girona. The age-specific rates (ASR) in Catalonia were estimated by an ASR average of Girona and Tarragona, that were adjusted by the standardized mortality ratio (SMR) of these health regions in relation to Catalonia. The cumulative rate and the risk of developing breast cancer were calculated, considering the probability of death by other causes. The temporal trend of breast cancer incidence was analysed by the Poisson's regression model. RESULTS: The cumulative risk (0-74 years) for breast cancer among Catalan women was 5.17% (1 out of 19 women). The highest risk of developing breast cancer is in the group of age between 60 and 79 years old. Tarragona and Girona had both a moderate increase that was not statistically significant. About 2,550 new cases of breast cancer have been estimated in 1994 and 2,600 in 1996. CONCLUSION: The risk of developing breast cancer in Catalonia after adjusting for the probability of dying by other causes, is lower than in other countries of Northern Europe and the United States.

The in vivo uptake of tritiated estradiol in carcinoma of the breast.

In human beings, the uptake of radiolabeled estradiol suppressed by carcinomatous breast tissue in vivo in relation to adipose breast tissue has been studied in 20 patients. The ratio of tumor uptake to fat tissue uptake was correlated with the age of the patient, menopausal status, presence of axillary metastases at time of mastectomy, and the response to endocrine therapy if metastases were presented. There was no correlation between a higher uptake of estradiol by the tumor and age of the patient, menopausal status, or presence of axillary metastases at time of mastectomy. Patients with a higher uptake of estradiol tended to respond favorably to endocrine treatment.

Estrogen binding protein of rat liver.

An estrogen binding protein for estradiol-17beta is present in the liver cytosol of female intact and one day oophorectomized rats. The dissociation constant reveals high affinity binding (Kd: 0.69 +/- 0.14 times 10(-10) M). Quantitation of EBP using a dextran-coated charcoal method shows that this specific macromolecular binding is much less than in the rat uterus, but similar to that in DMBA-induced mammary tumors. Sucrose density gradient analysis shows sedimentation at 8-9 S and 4-5 S when compared to bovine serum albumin.

[Sources of information about cancer]. / Las fuentes de información sobre el cáncer.

OBJECTIVE: To study the present and preferred sources of information about cancer. DESIGN: Cross-sectional study. PLACE: Counties of Gironés and Pla de l'Estany from the province of Girona. PARTICIPANTS: Stratified random sample of 408 women aged 40 to 70 years. RESULTS: Main present source of information about cancer were friends and relatives (34.9%), followed by radio and Tv (34.0%) and newspapers (19.9%). Health care professionals only were considered main source of information by 11.3% of the sample. Women with incomplete primary school and women from older age groups answered more frequently Radio and Tv as their main source of information. However, the preferred source of information about cancer were health care professionals (73.3%). CONCLUSION: Health care professionals are the preferred source of information about cancer but only a small percentage of population receive information from them. These results indicate the need to redefine educational strategies regarding cancer in primary health care.

Chemotherapy versus chemotherapy plus hormonotherapy in postmenopausal advanced breast cancer patients. A randomized trial.

One hundred seventeen postmenopausal advanced breast cancer patients previously untreated with chemotherapy were randomized to receive: cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), CMF and tamoxifen (TMX), and CMF and medroxyprogesterone (MAP). Treatments B and C induced a greater proportion of responses than treatment A. No effect was identified on the number of complete responses. After treatment failure, patients from groups A and C received Adriamycin (doxorubicin) (ADX) vincristine (VCR), and TMX and patients from group B received ADM, VCR, and MAP. No differences were found between the branches in the response rates to the second protocol. Responders to both treatments had a longer survival experience than nonresponders or responders to only one of the treatments. Survival was independent of the treatment group.

[Human papilloma virus in the etiology of cervicouterine cancer]. / El virus del papiloma humano en la etiología del cáncer cervicouterino.

The objectives of this study were to confirm the hypothesis that invasive carcinoma of the uterine cervix and the precursors of that condition are most often caused by human papilloma virus (HPV) infections, and to determine whether or not other risk factors are involved in the neoplastic process. For this purpose, four concurrent case-control studies were carried out. Two included cases of invasive cervical cancer and population-based controls. The other two included cases of in situ carcinoma and controls. Research was carried out in nine provinces of Spain and in Cali, Colombia. The identification of cases took place between June 1985 and June 1988. The studies included 436 incident cases of invasive carcinoma and 387 controls, selected at random from the corresponding populations, and 525 cases of in situ carcinoma and 512 controls paired by age, place of recruitment, and date that cytological specimens were taken from the women participating in cytological screening programs. Exposure to HPV was detected through hybridization tests after amplification by polymerase chain reaction (PCR) in exfoliated cervical cells from cases and controls. Exposure to HPV was the principal risk factor in the four studies. For invasive carcinoma, the relative risk and 95% confidence interval were 46.2 (18.5-115.1) in Spain and 15.6 (6.9-34.7) in Colombia. For in situ carcinoma, the figures were 56.9 (24.8-130.6) in Spain and 15.5 (8.2-29.4) in Colombia. This strong association was specific for types 16, 18, 31, 33, and 35 as well as still-unclassified HPV types.(ABSTRACT TRUNCATED AT 250 WORDS)

Cervical cancer and herpes simplex virus type 2: case-control studies in Spain and Colombia, with special reference to immunoglobulin-G sub-classes.

Two case-control studies, including 449 histologically confirmed cases of cervical intra-epithelial neoplasia (CIN) III and 425 controls, and 2 studies on invasive cervical cancer, involving 316 histologically confirmed cases and 330 population controls, were conducted in Colombia and Spain to assess the role of herpes simplex virus type 2 (HSV-2) in cervical neoplasia. Antibodies to this virus were also measured in the sera of 931 husbands of cases and controls. A serological assay using type-specific antigens, glycoprotein C for type I (gC-I) and glycoprotein G for type 2 (gG-2) was employed. Immunoglobulin-G (IgG) sub-classes, IgG1 and IgG3, were measured in women positive for HSV-2 antibodies. No increase in risk of CIN III or invasive cancer was found in women whose sera or whose husbands' sera were positive to HSV-2. However, compared with women negative to HSV-2, the risk of CIN III progressively increased with increasing levels of IgG1. The trend was statistically significant in Colombia. There was also a statistically significant increasing trend in risk of invasive cancer with levels of IgG1 in Spain. The levels of IgG3 and its ratio to IgG1, which may indicate recurrent infections, were not associated with the risk of either type of cancer. When the association with IgG1 was analyzed by human papillomavirus (HPV) DNA status, as determined by polymerase chain reaction, the trend was clearer in women whose HPV status was not determined or in those with negative HPV DNA. These results suggest that the role of HSV-2 is merely marginal and do not support the hypothesis that recurrent HSV-2 infections are of importance for cervical neoplasia.

The causal link between human papillomavirus and invasive cervical cancer: a population-based case-control study in Colombia and Spain.

To evaluate the association between human papillomavirus (HPV) and cervical cancer, we performed a population-based case-control study in Columbia and Spain, the former country having an incidence rate of cervical cancer about 8 times higher than the latter. It included 436 cases of histologically confirmed invasive cervical cancer and 387 randomly selected population controls. Information on demographic variables, sexual behaviour and other risk factors was obtained by interview. HPV-DNA was measured in cervical-swab specimens with 3 hybridization assays: ViraPap, Southern hybridization (SH) and polymerase chain reaction (PCR). The presence of HPV-DNA and detection of types 16, 18, 31, 33 and 35 were strongly associated with cervical cancer in each country regardless of the assay used. For both countries combined the adjusted odds ratios and 95% confidence intervals were: ViraPap OR = 25.9 (10.0-66.7); SH OR = 6.8 (3.4-13.4); and PCR OR = 28.8 (15.7-52.6). HPV-16 was the most common type detected in both cases and controls. Our results indicate that there is a very strong association between HPV 16, 18, 31, 33 and 35 and invasive cervical cancer and that this association is probably causal.